Pharmaceutical administration to neonates, infants and children

Abstract

The invention provides methods, devices and compositions for use in inhalation therapy of neonates, infants or children younger than 12 years, e.g. from 1 to 8 years, suffering from a disease, optionally a pulmonary disease, such as asthma, by which high amounts of inhaled drugs are directed to the small airways of the peripheral lungs of neonates, infants and children using slow, controlled flow rates and pre-set inhalation volumes. A novel inhalation device tailored for use in neonates, infants and children and adapted to provide said slow, controlled flow rates with a simplified jet nebuliser set-up is disclosed, together with kits comprising the device.

1 . A method of treatment of a subject being a neonate, infant, or child younger than 12 years suffering from a disease, optionally a pulmonary disease, the method comprising administering a composition as an aerosol,
 wherein said aerosol is comprised in a gas phase, and wherein said gas phase is administered to said subject:   (a) at a flow rate of from about 4 L/min to about 9 L/min during the inhalation period of the subject,   (b) at a total volume of about 0.10 L to about 0.80 L per inhalation, and   (c) wherein the gas phase comprising the aerosol is administered via an inhalation interface comprising a facemask and exhibiting a static dead volume (DV s ) between a nascent aerosol outlet at the upstream end of the inhalation interface and an outlet opening at the downstream end of the inhalation interface facing the subject's mouth of not more than 150 mL.   
     
     
         2 . The method according to  claim 1 , wherein the gas phase comprising the aerosol is generated by an inhalation device adapted to:
 (aa) emit the gas phase comprising the aerosol during the inhalation period of the subject at a flow rate of from about 4 L/min to about 9 L/min, and   (bb) emit, per inhalation, a total volume of about 0.10 L to about 0.80 L of the gas phase.   
     
     
         3 . The method according to  claim 1 , wherein the gas phase comprising the aerosol is administered during the inhalation period of the subject at a flow rate in the range of from about 4.8 L/min to about 7.2 L/min, and at a total volume of the gas phase in the range of from about 0.40 L to about 0.80 L. 
     
     
         4 . (canceled) 
     
     
         5 . The method according to  claim 1 , wherein the static dead volume (DV s ) is from about 1 mL to about 60 mL. 
     
     
         6 . The method according to  claim 1 , wherein the gas phase comprising the aerosol is administered via the facemask at an overpressure of up to about 10 mbar. 
     
     
         7 . The method according to  claim 1 , wherein the inhalation device comprises a jet nebuliser, a vibrating mesh nebuliser, or a spray nozzle nebuliser. 
     
     
         8 . The method according to  claim 1 , wherein the aerosol generator comprises a jet nebuliser operating at a nebulising pressure in the range of 1.6 bar to 2.0 bar. 
     
     
         9 . The method according to  claim 1 , wherein the disease is a pulmonary disease selected from the group bronchitis, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), pulmonary alveolar proteinosis (PAP), respiratory distress syndrome (RDS), acute bronchitis, bronchitis, bronchiectasis, primary ciliary dyskinesia, respiratory syncytial virus infection (RSV), chronic cough, or lung cancer. 
     
     
         10 . The method according to  claim 1 , wherein the composition comprises a glucocorticoid selected from budesonide, fluticasone propionate, beclomethasone dipropionate, ciclesonide, flunisolide, mometasone furoate, and triamcinolone acetonide. 
     
     
         11 . An inhalation device adapted to emit an inhalable pharmaceutical composition in the form of an aerosol comprised in a gas phase, the inhalation device comprising:
 (a) a facemask comprising an inhalation valve and an and an exhalation valve being configured to support an inhalation and/or an exhalation with positive pressure support with a pressure ranging from about 0.1 mbar to about 6 mbar,   (b) a jet nebuliser associated with an inhalation interface for generating the aerosol,   (c) an electronically controlled compressor for providing a flow of gas phase to said jet nebuliser, and   (d) an electronic controller,   adapted to directly control the operation of the electronically controlled compressor,   wherein the inhalation device is adapted to provide a complete gas phase comprising the aerosol through a nozzle of the jet nebuliser.   
     
     
         12 . The inhalation device according to  claim 11 , wherein the inhalation device is adapted to provide the complete gas phase comprising the aerosol through the nozzle of the jet nebuliser at a flow rate of from about 4 L/min to about 9 L/min. 
     
     
         13 . The inhalation device according to  claim 11 , wherein the inhalation device is adapted for the treatment of asthma in children to emit an inhalable pharmaceutical budesonide composition, and further adapted to deliver a dose in the range of from 10 μg to 70 μg at the facemask of the inhalation device. 
     
     
         14 . (canceled) 
     
     
         15 . A kit comprising the inhalation device according to  claim 11 , together with an inhalable pharmaceutical composition.